The use of radiotherapy in the treatment of cancer is based on the fact that ionizing radiation inhibits the proliferative capacity of tissues and results in cell death. The objective of this proposal is to study the effects of radiation in a related sequence of biochemical events which occur during the mammalian cell cycle and are involved in cell proliferation control. Previous studies have shown that the non-histone chromosomal proteins may be very important in the control of DNA replication, gene activation and cell division. The application proposes to study the effects of radiation on these proteins, as well as the enzymes and factors, specifically the protein kinases and cyclic nucleotides, which modify these proteins and possibly affect their regulatory functions. These studies should add fundamental insight to the understanding of radiation induced defects in cell cycle kinetics, and ultimately contribute to the optimization of the use of radiation for the treatment of human neoplastic disease.